CIL 2.1963 – Lex Salpensana, bronze tablet with a municipal law concerning citizenship and manumission

Photograph and translation

CIL 2.1964 – Lex Malacitana, bronze tablet with a municipal law

Photograph and translation

Compression stockings and the prevention of symptomatic venous thromboembolism: data from the Tinzaparin in Acute Ischaemic Stroke Trial

Background: Venous thromboembolism (VTE) is a well recognised and preventable complication of acute stroke. While graduated compression stockings reduce the risk of VTE in surgical patients their benefit in acute stroke remains uncertain. Methods: The relationship between symptomatic VTE and use of stockings using observational data from the ‘Tinzaparin in Acute Ischaemic Stroke Trial’, which compared 10 days of treatment with tinzaparin (175 IU.kg-1 or 100 IU.kg-1) with, aspirin (300 mg od), was assessed using logistic regression adjusted for known VTE risk factors and treatment. Results: Symptomatic VTE occurred in 28 patients (1.9%, DVT 18, PE 13) within 15 days of enrolment in 1,479 patients. Patients wearing one or two stockings for any period of time during the first 10 days (n=803) had a non-significant increase (odds ratio, OR 2.45, 95% confidence interval, CI 0.95 - 6.32) in the risk of symptomatic VTE. In contrast, those wearing bilateral stockings for 10 days (n=374) had a non-significant reduction in the odds of symptomatic VTE as compared to those who wore no stockings or wore them for less than 10 days (OR 0.65, 95% CI 0.26-1.65). Mild stroke and treatment with tinzaparin were associated with a reduced risk of VTE. Conclusions: Bilateral graduated compression stockings may reduce the incidence of VTE by one-third in patients with acute ischaemic stroke. However, the uncertainty in this finding, low frequency of symptomatic VTE, potential for stockings to cause harm, and cost of stockings highlight the need for a large randomised-controlled trial to examine the safety and efficacy of stockings in acute stroke.

3D Porous Architecture of Stacks of β-TCP Granules Compared with That of Trabecular Bone: A microCT, Vector Analysis, and Compression Study

International audience

The impact of mechanical compression on cortical microtubules in Arabidopsis: a quantitative pipeline

Exogenous mechanical perturbations on living tissues are commonly used to investigate whether cell effectors can respond to mechanical cues. However, in most of these experiments, the applied mechanical stress and/or the biological response are described only qualitatively. We developed a quantitative pipeline based on microindentation and image analysis to investigate the impact of a controlled and prolonged compression on microtubule behaviour in the Arabidopsis shoot apical meristem, using microtubule fluorescent marker lines. We found that a compressive stress, in the order of magnitude of turgor pressure, induced apparent microtubule bundling. Importantly, that response could be reversed several hours after the release of compression. Next, we tested the contribution of microtubule severing to compression-induced bundling: microtubule bundling seemed less pronounced in the katanin mutant, in which microtubule severing is dramatically reduced. Conversely, some microtubule bundles could still be observed 16 hours after the release of compression in the spiral2 mutant, in which severing rate is instead increased. To quantify the impact of mechanical stress on anisotropy and orientation of microtubule arrays, we used the nematic tensor based FibrilTool ImageJ/Fiji plugin. To assess the degree of apparent bundling of the network, we developed several methods, some of which were borrowed from geostatistics. The final microtubule bundling response could notably be related to tissue growth velocity that was recorded by the indenter during compression. Because both input and output are quantified, this pipeline is an initial step towards correlating more precisely the cytoskeleton response to mechanical stress in living tissues.

Development and optimization of fluoxetine orally disintegrating tablets using Box-Behnken design

Purpose: To develop and optimise some variables that influence fluoxetine orally disintegrating tablets (ODTs) formulation. Methods: Fluoxetine ODTs tablets were prepared using direct compression method. Three-factor, 3- level Box-Behnken design was used to optimize and develop fluoxetine ODT formulation. The design suggested 15 formulations of different lubricant concentration (X1), lubricant mixing time (X2), and compression force (X3) and then their effect was monitored on tablet weight (Y1), thickness (Y2), hardness (Y3), % friability (Y4), and disintegration time (Y5). Results: All powder blends showed acceptable flow properties, ranging from good to excellent. The disintegration time (Y5) was affected directly by lubricant concentration (X1). Lubricant mixing time (X2) had a direct effect on tablet thickness (Y2) and hardness (Y3), while compression force (X3) had a direct impact on tablet hardness (Y3), % friability (Y4) and disintegration time (Y5). Accordingly, Box-Behnken design suggested an optimized formula of 0.86 mg (X1), 15.3 min (X2), and 10.6 KN (X3). Finally, the prediction error percentage responses of Y1, Y2, Y3, Y4, and Y5 were 0.31, 0.52, 2.13, 3.92 and 3.75 %, respectively. Formula 4 and 8 achieved 90 % of drug release within the first 5 min of dissolution test. Conclusion: Fluoxetine ODT formulation has been developed and optimized successfully using Box- Behnken design and has also been manufactured efficiently using direct compression technique.

Bioequivalence evaluation of new microparticulate capsule and marketed tablet dosage forms of lornoxicam in healthy volunteers

Purpose: To compare oral bioavailability and pharmacokinetic parameters of different lornoxicam formulations and to assess similarity in plasma level profiles by statistical techniques. Methods: An open-label, two-period crossover trial was followed in 24 healthy Pakistani volunteers (22 males, 2 females). Each participant received a single dose of lornoxicam controlled release (CR) microparticles and two doses (morning and evening) of conventional lornoxicam immediate release (IR) tablet formulation. The microparticles were prepared by spray drying method. The formulations were administered again in an alternate manner after a washout period of one week. Pharmacokinetic parameters were determined by Kinetica 4.0 software using plasma concentration-time data. Moreover, data were statistically analyzed at 90 % confidence interval (CI) and Schuirmann’s two one-sided t-test procedure. Results: Peak plasma concentration (Cmax) was 20.2 % lower for CR formulation compared to IR formulation (270.90 ng/ml vs 339.44 ng/ml, respectively) while time taken to attain Cmax (tmax) was 5.25 and 2.08 h, respectively. Area under the plasma drug level versus time (AUC) curve was comparable for both CR and IR formulations. The 90 % confidence interval (CI) values computed for Cmax, AUC0-24, and AUC0-∞ , after log transformation, were 87.21, 108.51 and 102.74 %, respectively, and were within predefined bioequivalence range (80 - 125 %). Conclusion: The findings suggest that CR formulation of lornoxicam did not change the overall pharmacokinetic properties of lornoxicam in terms of extent and rate of lornoxicam absorption.

Development of two charge transfer complex spectrophotometric methods for determination of tofisopam in tablet dosage form

Purpose: To develop a simple, fast and sensitive spectrophotometric method for the determination of tofisopam in tablet dosage form. Methods: Tofisopam as n-electron donor was reacted with two π-acceptors, namely, chloranilic acid (ChA), and 7,7,8,8 tetracyanoquinodimethane (TCNQ) to form charge transfer complexes. The complexes were evaluated spectrophotometrically at 520 and 824 nm for ChA and TCNQ, respectively. The optimum conditions for the reaction were determined and optimized. The developed method was compared with Japanese Pharmacopeia method. Results: The calibration curve was linear in the ranges 25 – 125 and 30 – 150 μg/mL for ChA and TCNQ, respectively. The lower limit of detection was 8.0 and 10.0 μg/mL for ChA and TCNQ, respectively while the slope and intercept of the calibration curves were 0.0025 and 0.011 and 0.0115 and -0.237, for ChA and TCNQ, respectively. Conclusion: The developed methods for tofisopam have good accuracy and precision, and comparable to a standard pharmacopeial method. The methods can be applied for routine analysis and in quality control.

Liquid chromatographic-mass spectrometric method for determination of drug content uniformity of two commonly used dermatology medications in a split-tablet dosage form

Purpose: To develop and validate a simple, efficient and reliable Liquid chromatographic-mass spectrometric (LC-MS/MS) method for the quantitative determination of two dermatological drugs, Lamisil® (terbinafine) and Proscar® (finasteride), in split tablet dosage form. Methods: Thirty tablets each of the 2 studied medications were randomly selected. Tablets were weighed and divided into 3 groups. Ten tablets of each drug were kept intact, another group of 10 tablets were manually split into halves using a tablet cutter and weighed with an analytical balance; a third group were split into quarters and weighed. All intact and split tablets were individually dissolved in a water: methanol mixture (4:1), sonicated, filtered and further diluted with mobile phase. Optimal chromatographic separation and mass spectrometric detection were achieved using an Agilent 1200 HPLC system coupled with an Agilent 6410 triple quadrupole mass spectrometer. Analytes were eluted through an Agilent eclipse plus C8 analytical column (150 mm × 4.6 mm, 5 μm) with a mobile phase composed of solvent A (water) containing 0.1% formic acid and 5mM ammonium formate pH 7.5, and solvent B (acetonitrile mixed with water in a ratio A:B 55:45) at a flow rate of 0.8 mL min-1 with a total run time of 12 min. Mass spectrometric detection was carried out using positive ionization mode with analyte quantitation monitored by multiple reaction monitoring (MRM) mode. Results: The proposed analytical method proved to be specific, robust and adequately sensitive. The results showed a good linear fit over the concentration range of 20 - 100 ng mL-1 for both analytes, with a correlation coefficient (r2) ≥ 0.999 and 0.998 for finasteride and terbinafine, respectively. Following tablet splitting, the drug content of the split tablets fell outside of the proxy USP specification for at least 14 halves (70 %) and 34 quarters (85 %) of FIN, as well as 16 halves (80 %) and 37 quarters (92.5 %) of TBN. Mean weight loss, after splitting, was 0.58 and 2.22 % for FIN half- and quarter tablets, respectively, and 3.96 and 4.09 % for TBN half- and quarter tablets,respectively. Conclusion: The proposed LC-MS/MS method has successfully been used to provide precise drug content uniformity of split tablets of FIN and TBN. Unequal distribution of the drug on the split tablets is indicated by the high standard deviation beyond the accepted value. Hence, it is recommended not to split non-scored tablets especially, for those medications with significant toxicity

Nonlinear combining and compression in multicore fibers

We demonstrate numerically light-pulse combining and pulse compression using wave-collapse (self-focusing) energy-localization dynamics in a continuous-discrete nonlinear system, as implemented in a multicore fiber (MCF) using one-dimensional (1D) and 2D core distribution designs. Large-scale numerical simulations were performed to determine the conditions of the most efficient coherent combining and compression of pulses injected into the considered MCFs. We demonstrate the possibility of combining in a single core 90% of the total energy of pulses initially injected into all cores of a 7-core MCF with a hexagonal lattice. A pulse compression factor of about 720 can be obtained with a 19-core ring MCF.

O Tablet como recurso promotor da aprendizagem funcional de alunos com multideficiência

O projeto que aqui se apresenta surge no âmbito do mestrado em Educação Especial, no Domínio Cognitivo e Motor, e insere-se na área da multideficiência. O termo multideficiência designa um conjunto de limitações acentuadas no domínio cognitivo, associadas a limitações acentuadas noutros domínios, nomeadamente no domínio motor, sensorial e/ou da saúde física. Desta forma, o termo multideficiência, por si só, não define o indivíduo. Todas as crianças e jovens têm necessidades individuais, o planeamento das atividades para alunos com multideficiência requerem uma maior interação entre os profissionais que trabalham com o aluno e o próprio aluno. O presente estudo foi implementado no Agrupamento de Escolas Dr. Correia Mateus, na Unidade de Apoio Especializado para a Educação de Alunos com Multideficiência e Surdocegueira Congénita do segundo e terceiro ciclos do Ensino Básico. O objetivo geral do estudo é analisar de que forma a tecnologia tátil promove a aprendizagem funcional de alunos com multideficiência, tendo sido utilizado como recurso o Tablet ‘comum’, sem adaptações. Os resultados demonstraram que o equipamento tátil constituiu o elemento promotor de aprendizagem funcional através da aplicação de estratégias, como a implementação de jogos pedagógicos interativos e da aprendizagem pela repetição, que permitiram o desenvolvimento de competências adaptadas às necessidades e às especificidades dos alunos, proporcionando o seu desenvolvimento individual e social, melhorando a sua qualidade de vida, melhorando a sua autonomia e, consequentemente, favorecendo a inclusão.

Optimisation thermodynamique d’un procédé solaire utilisant un système de réfrigération à éjecto-compression pour la production du froid

L’objectif essentiel de cette thèse est de développer un système industriel de réfrigération ou de climatisation qui permet la conversion du potentiel de l’énergie solaire en production du froid. Ce système de réfrigération est basé sur la technologie de l’éjecto-compression qui propose la compression thermique comme alternative économique à la compression mécanique coûteuse. Le sous-système de réfrigération utilise un appareil statique fiable appelé éjecteur actionné seulement par la chaleur utile qui provient de l’énergie solaire. Il est combiné à une boucle solaire composée entre autres de capteurs solaires cylindro-paraboliques à concentration. Cette combinaison a pour objectif d’atteindre des efficacités énergétiques et exergétiques globales importantes. Le stockage thermique n’est pas considéré dans ce travail de thèse mais sera intégré au système dans des perspectives futures. En première étape, un nouveau modèle numérique et thermodynamique d’un éjecteur monophasique a été développé. Ce modèle de design applique les conditions d’entrée des fluides (pression, température et vitesse) et leur débit. Il suppose que le mélange se fait à pression constante et que l’écoulement est subsonique à l’entrée du diffuseur. Il utilise un fluide réel (R141b) et la pression de sortie est imposée. D’autre part, il intègre deux innovations importantes : il utilise l'efficacité polytropique constante (plutôt que des efficacités isentropiques constantes utilisées souvent dans la littérature) et n’impose pas une valeur fixe de l'efficacité du mélange, mais la détermine à partir des conditions d'écoulement calculées. L’efficacité polytropique constante est utilisée afin de quantifier les irréversibilités au cours des procédés d’accélérations et de décélération comme dans les turbomachines. La validation du modèle numérique de design a été effectuée à l’aide d’une étude expérimentale présente dans la littérature. La seconde étape a pour but de proposer un modèle numérique basé sur des données expérimentales de la littérature et compatible à TRNSYS et un autre modèle numérique EES destinés respectivement au capteur solaire cylindro-parabolique et au sous-système de réfrigération à éjecteur. En définitive et après avoir développé les modèles numériques et thermodynamiques, une autre étude a proposé un modèle pour le système de réfrigération solaire à éjecteur intégrant ceux de ses composantes. Plusieurs études paramétriques ont été entreprises afin d’évaluer les effets de certains paramètres (surchauffe du réfrigérant, débit calorifique du caloporteur et rayonnement solaire) sur sa performance. La méthodologie proposée est basée sur les lois de la thermodynamique classique et sur les relations de la thermodynamique aux dimensions finies. De nouvelles analyses exergétiques basées sur le concept de l’exergie de transit ont permis l'évaluation de deux indicateurs thermodynamiquement importants : l’exergie produite et l’exergie consommée dont le rapport exprime l’efficacité exergétique intrinsèque. Les résultats obtenus à partir des études appliquées à l’éjecteur et au système global montrent que le calcul traditionnel de l’efficacité exergétique selon Grassmann n’est désormais pas un critère pertinent pour l'évaluation de la performance thermodynamique des éjecteurs pour les systèmes de réfrigération.

Vocabulary Transfer and Knowledge Distillation for Language Model Compression

Natural Language Processing (NLP) has seen tremendous improvements over the last few years. Transformer architectures achieved impressive results in almost any NLP task, such as Text Classification, Machine Translation, and Language Generation. As time went by, transformers continued to improve thanks to larger corpora and bigger networks, reaching hundreds of billions of parameters. Training and deploying such large models has become prohibitively expensive, such that only big high tech companies can afford to train those models. Therefore, a lot of research has been dedicated to reducing a model’s size. In this thesis, we investigate the effects of Vocabulary Transfer and Knowledge Distillation for compressing large Language Models. The goal is to combine these two methodologies to further compress models without significant loss of performance. In particular, we designed different combination strategies and conducted a series of experiments on different vertical domains (medical, legal, news) and downstream tasks (Text Classification and Named Entity Recognition). Four different methods involving Vocabulary Transfer (VIPI) with and without a Masked Language Modelling (MLM) step and with and without Knowledge Distillation are compared against a baseline that assigns random vectors to new elements of the vocabulary. Results indicate that VIPI effectively transfers information of the original vocabulary and that MLM is beneficial. It is also noted that both vocabulary transfer and knowledge distillation are orthogonal to one another and may be applied jointly. The application of knowledge distillation first before subsequently applying vocabulary transfer is recommended. Finally, model performance due to vocabulary transfer does not always show a consistent trend as the vocabulary size is reduced. Hence, the choice of vocabulary size should be empirically selected by evaluation on the downstream task similar to hyperparameter tuning.